Crosstalk between microglia and neural stem cells influences the relapse of glioblastoma in GBM immunological microenvironment

Xingliang Dai; Lei Ye; Huaixu Li; Xuchen Dong; Haotian Tian; Peng Gao; Jun Dong; Hongwei Cheng

doi:10.1016/j.clim.2023.109333

Crosstalk between microglia and neural stem cells influences the relapse of glioblastoma in GBM immunological microenvironment

Clin Immunol. 2023 Jun:251:109333. doi: 10.1016/j.clim.2023.109333. Epub 2023 Apr 23.

Authors

Xingliang Dai¹, Lei Ye¹, Huaixu Li¹, Xuchen Dong², Haotian Tian¹, Peng Gao³, Jun Dong⁴, Hongwei Cheng⁵

Affiliations

¹ Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China.
² Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China.
³ Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address: gaopeng@ahmu.edu.cn.
⁴ Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China. Electronic address: dongjun@suda.edu.cn.
⁵ Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China. Electronic address: hongwei.cheng@ahmu.edu.cn.

PMID: 37088298
DOI: 10.1016/j.clim.2023.109333

Abstract

Interactions between immunocytes and Neural Stem Cells (NSCs) in glioblastoma multiforme still remains unclear. Here, microglial cells and NSCs in peri-tumoral tissue were analyzed via single-cell whole-transcriptome sequencing. Results showed that two clusters of putative NSCs (the EGFR⁺BCAN⁺ cell cluster, and the FABPT⁺H19⁺ cell cluster) exhibited immune-related functions. Two clusters of putative microglia (the XIST⁺PDK4⁺ and APOC1⁺CCL3⁺ cell clusters) exhibited the function of glial cell activation. The results of ligand receptor network analysis disclosed significant interactions between the APOC1⁺CCL3⁺ microglia and the NSCs. Correlation analysis on the overall survival (OS) and relapse-free survival (RFS) with 102 potential molecular targets in the TCGA database showed that a much larger number of molecules were correlated with RFS than with OS (34.31% vs. 8.82%), nine of them were validated in clinical specimens. In conclusion, crosstalk between APOC1⁺CCL3⁺ microglia and multiple molecule-labeled NSCs distal to the tumor core play certain roles on the recurrence of GBM.

Keywords: Glioblastoma multiforme; Immunological microenvironment; Recurrence; Single-cell RNA sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / pathology
Glioblastoma* / pathology
Humans
Microglia / pathology
Neoplasm Recurrence, Local
Neural Stem Cells* / pathology
Tumor Microenvironment